Recent advances in the treatment and monitoring of HIV-1 infection have substantially diminished HIV-associated illness and mortality; however the management of HIV-infected patients has become increasingly complex. We are conducting studies that: (1) define the Hepatitis C viral response to pegylated interferon-based therapy in HIV co-infected individuals (2) evaluate novel therapeutic strategies in the management of Hepatitis C virus in HIV co-infected individuals, and (3) develop novel genomic and proteomic markers that predict Hepatitis C viral response to existing and novel therapies. Analyses of the kinetics of the viral response to standard Hepatitis C therapy in Hepatitis C/HIV co-infected individuals suggest that it may be possible to predict a long term response to anti-Hepatitis C therapy based on the initial response to therapy of Hepatitis C virus levels in plasma. Using combination therapy of pegylated interferon together with ribavirin in these subjects, we are determining whether genomic and proteomic markers can predict response to therapy prior to initiation of treatment. Subsequent clinical trials will determine whether more frequent doses of pegylated interferon in combination with ribavirin enhance the viral kinetic response to Hepatitis C therapy in persons co-infected with Hepatitis C and HIV. A new clinical trial using albumin-conjugated interferon alpha (Alb-Interferon) to treat Hepatitis C in HIV-infected patients will begin enrollment later this year.